Multiple paraganglioma syndrome type 4 due to succinate dehydrogenase B mutation: diagnostic and therapeutic challenges of a skull base paraganglioma masquerading as nasopharyngeal cancer.

Objective: To report a case of hereditary paraganglioma and describe the underlying genetic mutation and response to iodine 131 metaiodobenzylguanidine (MIBG) therapy.

Methods: We describe the clinical course and laboratory and imaging findings of the study patient.

Results: A 38-year-old man presented in May 2005 with pseudobulbar palsy and was initially thought to have nasopharyngeal cancer because computed tomography of the head showed a large, locally invasive nasopharyngeal tumor. During tumor staging, abdominal computed tomography showed a large, locally invasive left adrenal tumor. Urinary normetanephrine was extremely elevated at 39,831 microg/24 h (reference range, 0-580 microg/24 h), while metanephrine was normal. MIBG scan showed uptake in the left adrenal gland and in the skull mass. Biopsy of the nasopharyngeal mass confirmed the diagnosis of paraganglioma. The patient underwent resection of the 13-cm pheochromocytoma in the left adrenal gland, with resection of part of the colon and kidney. Postoperatively, urinary normetanephrine dropped to 9339 microg/24 h. The nasopharyngeal paraganglioma was inoperable. The patient was treated with 3 doses of MIBG-201, 190, and 225 mCi in August 2007, January 2008, and January 2009, respectively. Urinary normetanephrine normalized, and follow-up magnetic resonance imaging showed a 60% reduction in the size of the nasopharyngeal tumor. Genetic testing revealed a C to T transition at nucleotide 268 in exon 3 of the SDHB gene, resulting in a change from an arginine to a stop codon (Arg90X) and leading to a truncated SDHB protein.

Conclusions: This case illustrates the diagnostic and therapeutic challenges of hereditary paraganglioma and the value of genetic testing. It also demonstrates the effectiveness of MIBG therapy for inoperable paragangliomas.